Immunogenicity, Efficacy and Safety Study of an MSP3-LSP (Long Synthetic Peptide) Malaria Vaccine

• Number of clinical malaria episodes occurring during the consecutive malaria transmission season after the third vaccination [ Time Frame: 27 Months ] [ Designated as safety issue: No ]
  

• Solicited adverse events measured from day 0 to day 7 after each dose [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  
• Unsolicited adverse events measured up to one month after each dose [ Time Frame: Day 84 ] [ Designated as safety issue: Yes ]
  
• Serious Adverse Events measured during the 12 months of study duration [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  
• The humoral response to the vaccine antigen: assessed by measuring the level of IgG by ELISA [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
  
• IgG ability to recognize the native protein on Merozoite using Western Blot(WB) method [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
  
• Incidence of all clinical malaria episodes occurring through two transmission seasons subsequent to the 3 doses. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

This will be a double blind, randomized, placebo-controlled phase IIb study to evaluate the immunogenicity, efficacy and safety of Plasmodium falciparum vaccine candidate, Merozoite Surface Protein-3 Long synthetic peptide (MSP3) adjuvanted in aluminium hydroxide versus Verorab control in healthy children aged 12-48 months in Mali

A phase Ib trial is currently ongoing in Burkina Faso as well as in Tanzania and its interim results inform on the best dose/adjuvant combination to be safely extended in younger children. The trial is evaluating immunogenicity,efficacy and safety of 3 doses of 30 µg MSP3 adjuvanted in aluminium hydroxide

Primary objective:

• To assess the efficacy of MSP3-LSP:
• Determine the efficacy of MSP3-LSP in children aged 12-48 months against all clinical malaria episodes (Axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia) occurring during the consecutive malaria transmission season after the third vaccination (six months after the third vaccination).

Secondary Objectives:

• To assess the safety and reactogenicity of 3 doses of 30 µg MSP3 adjuvanted in aluminum hydroxide given at D0, D28 and D56 in healthy children aged 12-48 months old in Mali.
• To assess IgG ability to recognize the native protein on Merozoite by using Western Blot (WB) method, and measure efficacy among the subgroup of individuals able to react with parasite proteins in WB.
• To assess the humoral immune response to the vaccine antigen using ELISA.
• Determine the efficacy of MSP3 in children aged 12-48 months against first clinical malaria episodes.
• To assess the efficacy of MSP3-LSP in children aged 12-48 months against all clinical malaria episodes occurring during the ensuing TWO years

Exploratory Objectives:

To further characterize the MSP3 vaccine efficacy by measuring:

• Relationship between efficacy and serological responses induced by the vaccine
• Duration of protection over the period of two years
• Vaccine efficacy against disease defined by various parasite thresholds [500, 2500, 5000, 10,000 and 20,000/µL]
• Vaccine efficacy against severe malaria disease
• Vaccine efficacy against anaemia
• To evaluate functionality of IgG by using the ADCI technique
• To assess the cellular T-helper type 1 immune responses to the vaccine antigens by Elispot, and their persistence over 24 months of follow-up

The primary evaluation will include the following:

Solicited adverse events measured from day 0 to day 7 after each dose; Unsolicited adverse events measured up to one month after each dose; Serious Adverse Event (SAE) measured during the 12 months of study duration. Passive and active case detection will be used to capture all adverse events including clinical malaria episodes. After third dose. All participants will go through the scheduled clinic visits on days 84, 168, 365, 540 and 730 for clinical assessment. Children will be followed for two years following the first vaccination. During scheduled visits malaria smear and hemoglobin will be done systematically on days 0, 28, 56, 84, 168, 365, 540 and 730. The humoral immune response to the vaccine antigen will be assessed using ELISA on days 0, 28, 56, 84, 168, 365, 540 and 730. Cellular immune response to the vaccine antigens will be assessed on days 0, 56, 84, 168, 540 and 730 using Elispot to MSP3-LSP. The functionality of the induced immune responses using Western Blot (WB) method and ADCI technique will be evaluated on days 0, 84, 168, 365, 540 and 730.

Biological safety: two and four weeks after each vaccination, and thereafter every 12 weeks, in reference with the baseline before the first dose, by measuring the following RBC, hemoglobin, hematocrit, platelets, WBC with differential counts, ASAT, ALAT, total bilirubin, alkaline phosphatase, γGT, creatinin.

Statistical methods:

Descriptive methods shall be employed to evaluate the above criteria.